Barrier catheter apparatus and method

ABSTRACT

A catheter for use in delivery or withdrawal of a formulation, wherein the catheter has an outer layer comprising a bio-compatible material and a barrier layer comprising a material that provides a more effective barrier than the outer layer against inward and outward diffusion of substances that may cause destabilization of the formulation. The outer surface of the barrier layer contacts at least a portion of the inner surface of the outer layer. The catheter may include a flared distal end tip to aid in the release, during a bolus delivery or catheter flush, of any obstruction situated at the distal end tip of the catheter. The larger cross-sectional area at the flared distal end tip minimizes the chances that any obstruction that develops at the distal end tip will be sufficient to hinder the flow of the formulation within the lumen of the catheter. The catheter may also include a slit valve at the distal end tip which has one or more and, preferably a plurality of slits that may be elastically extended to an open position by the expulsion of the formulation during an IIP pump stroke. During the interval between IIP pump strokes, the slits return to a closed position and hinder the inflow of body fluid into the distal end tip.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] Embodiments of the present invention claim priority from a U.S.Provisional Application entitled “Barrier Catheter Apparatus andMethod,” Serial No. 60/317,358, filed Sep. 5, 2001, the contents ofwhich are incorporated by reference herein, and relate to copending U.S.Patent Application “Stabilizing Catheter For Protein Drug Delivery,”attorney docket No. 047711/0273, filed concurrently herewith, thecontents of which are incorporated by reference herein.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates, generally, to improvements incatheters, and, in preferred embodiments, to a catheter thatsignificantly reduces diffusion of substances through the catheter walland, in further preferred embodiments, possibly hinders the formation ofobstructions in the distal end tip of the catheter.

[0004] 2. Description of Related Art

[0005] In the medical arts, catheters are used to inject fluids into ordrain fluids away from the body. Catheters may be used in combinationwith a device such as a pump, which is implanted in the body of apatient, the pump being suitable for the programmed delivery of measureddoses of a formulation. (A formulation is defined in the presentdisclosure as the substance being conveyed by the catheter. Thissubstance may comprise either a mixture of different components or itmay be a single, pure substance.) A typical example of such use is theintraperitoneal delivery of an insulin formulation. FIG. 1 illustratesan example of this use. As shown in FIG. 1, an implantable infusion pump(IIP) 10 is implanted in a patient below the skin and above the musclein the abdomen. The IIP 10 will then dispense an infusion formulation(such as an insulin formulation) through the peritoneum wall 12 via acatheter 14. A lead 16 may connect IIP 10 to a sensing device (notshown) that is used to regulate the delivery of the infusionformulation.

[0006] Depending on the circumstances, it may be necessary or desirablethat the IIP and catheter remain within the patient for extended timeperiods ranging from a number of days to a number of years. Thus, thecatheter is exposed to the body fluids of the patient. Substances withinthese body fluids can, over time, diffuse through the catheter wall andinteract with the infusion formulation within the lumen of the catheter.The diffusion of certain molecules may lead to the formation of catheterobstructions. For example, it is believed that diffusion of one or moremolecules (for example, of CO₂ and/or phenol) through the wall of acatheter carrying an insulin formulation may lead to precipitation andeventually to the formation of deposits that may result in catheterobstructions. In addition, obstructions often form at the distal end tipof the catheter, possibly as a result of CO₂ mixing with the infusionformulation that is present near the tip, especially during the intervalbetween pump strokes of the IIP.

[0007] An additional problem with inward diffusion of molecules throughthe wall of a catheter is that the molecules interact with the infusionformulation. Thus, the composition of the infusion formulation withinthe catheter may be destabilized. This makes it difficult to accuratelycontrol the properties, composition, and/or stability of the infusionformulation delivered to the infusion site.

[0008] Along with the problem of diffusion of molecules through the wallinto the catheter is the related problem of outward diffusion ofmolecules of the infusion formulation components through the wall of thecatheter and into the patient at other than the infusion site. Forexample, when an insulin formulation is being conveyed by a catheter,preservatives within the insulin formulation, such as phenol andm-cresol, may diffuse out of the catheter. Again, as a result of thisoutward diffusion, the properties, composition, and/or stability of theinfusion formulation delivered to the infusion site will be difficult tocontrol. Furthermore, it is believed that the diffusion of phenol fromthe insulin formulation destabilizes the insulin formulation and has atendency to precipitate and lead to the formation of catheterobstructions.

[0009] As the technology improves, implant devices such as the IIP arebecoming smaller. Because of the smaller size of the IIP, only a smallervolume of the infusion formulation can be accommodated within the IIP.Thus, higher concentration infusion formulations are normally used. Withhigher concentration infusion formulations, it is even more importantthat the properties, composition, and/or stability of the infusionformulation are accurately controlled.

[0010] An exemplary catheter comprises a lumen which extends through aninner wall of polyethylene and a relatively flexible outer wall ofbio-compatible polymer material such as silicone rubber. The lumen isthe medium through which the infusion formulation will pass. The distalend of the catheter is usually located at an infusion site. The proximalend of the catheter is usually attached to a source of the infusionformulation, which may be within an IIP.

[0011] An exemplary catheter, as discussed above, may comprise an innerwall of polyethylene and an outer wall of silicone rubber. Both of thesematerials can be insufficient barriers to diffusion. In addition, theexemplary catheter discussed above allows a infusion formulation to beresident in the catheter for long periods of time before it is dispensedfrom the distal end. CO₂ and other substances present in body fluids maydiffuse and/or mix with the infusion formulation in the distal end tipand cause obstructions to form.

[0012] Accordingly, there is a demand for a catheter that restrictsdiffusion into or out of the catheter walls. There is also a demand fora catheter that will reduce the chances that the infusion formulationflowing through the lumen will be hindered by obstructions in the distalend tip of the catheter.

SUMMARY OF THE DISCLOSURE

[0013] Therefore, it is an advantage of embodiments of the presentinvention to provide a catheter which provides a significant barrier todiffusion of CO₂ and other substances into the lumen of the catheter.

[0014] It is a further advantage of embodiments of the present inventionto provide a catheter that inhibits diffusion of preservatives and othersubstances within an infusion formulation outward through the walls ofthe catheter and into the body of the patient before reaching the distalend of the catheter.

[0015] It is a further advantage of embodiments of the present inventionto provide a catheter which inhibits deposit formation that can tend tooccur at or near the distal end tip and facilitates the expulsion duringdelivery, for example, delivery of a bolus or catheter flush.

[0016] These and other advantages are accomplished according to acatheter which provides a significant barrier to inward diffusion of anyundesirable substance into the lumen of the catheter and/or to outwarddiffusion of any infusion formulation contained within the lumen of thecatheter.

[0017] In a preferred embodiment of the present invention, a barrierlayer is provided within the catheter that is comprised of materialwhich has a lower permeability than conventional materials used in thewall of a catheter. Thus, preferably, the barrier layer material has alower permeability for molecules in the infusion formulation and in theenvironment of use than conventional materials used in the wall of acatheter. Thus, the properties, composition, and/or stability of theinfusion formulation delivered to the infusion site may be moreaccurately controlled. In one preferred embodiment, the undesirablesubstance is believed to be CO₂ and the infusion formulation comprisesan insulin formulation.

[0018] Preferred embodiments of the present invention also provide acatheter which inhibits deposit formation at the distal end tip andfacilitates the expulsion during delivery of a bolus or catheter flush.According to one embodiment, a flared distal end tip aids in therelease, during a bolus delivery or catheter flush, of any obstructionsituated at the distal end tip of the catheter. The largercross-sectional area of the inner channel of the lumen at the flareddistal end tip minimizes the chances that any obstruction that developsat or near the distal end tip will be sufficient to hinder the flow ofthe infusion formulation within the lumen of the catheter. In addition,deposits that do form in the flared portion of the distal end tip aremore likely to be expelled during a bolus delivery or catheter flush dueto the shape and larger cross-sectional area of the flare.

[0019] Further preferred embodiments of the present invention alsoprovide a catheter which inhibits deposit formation at or near thedistal end tip by providing a slit valve that greatly reduces thepotential for obstructions resulting from the mixing of body fluids withthe infusion formulation during the interval between pump strokes of aninfusion pump. The slit valve comprises a portion of the outer layermaterial extended over the distal end with one or more and, preferably aplurality of slits that may be elastically extended to an open positionby the expulsion of the infusion formulation during a pump stroke of theinfusion pump. During the interval between pump strokes, the slits willreturn to a closed position and hinder the inflow of body fluid into thedistal end tip.

[0020] Further preferred embodiments of the present invention comprise acatheter which provides an annular channel to aid in the delivery of theinfusion formulation to the infusion site in the event of an obstructionat or near the distal end tip of the catheter. This annular channel isformed in the layers of the catheter at a sufficient upstream distancefrom the distal end tip to provide an alternate passageway, undersufficient pressure, for the infusion formulation to flow to theinfusion site through the annular channel.

[0021] Depending upon the context of use, the invention may includevarious combinations of these features which function together toprovide protection against diffusion of substances through the catheterlayers and against the formation of catheter obstructions. Variousembodiments of the invention include one or more of these features.Preferred embodiments of the present invention contain each of thesefeatures.

[0022] These and other objects, features, and advantages of embodimentsof the invention will be apparent to those skilled in the art from thefollowing detailed description of embodiments of the invention, whenread with the drawings and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Referring now to the drawings in which like reference numbersrepresent corresponding parts throughout:

[0024]FIG. 1 shows a fragmented cutaway view of an exemplary environmentof use of the present invention for the intraperitoneal delivery of aninsulin formulation.

[0025]FIG. 2 illustrates a fragmented cutaway view of an example of acatheter with a barrier layer according to an embodiment of theinvention.

[0026]FIG. 3 illustrates an example of a catheter with a flared distalend tip according to an embodiment of the invention.

[0027]FIG. 4 illustrates a fragmented cutaway view of an example of acatheter with a slit valve at the distal end tip according to anembodiment of the invention.

[0028]FIG. 5 illustrates a fragmented cutaway view of an example of acatheter with an annular channel according to an embodiment of theinvention.

[0029]FIG. 6 illustrates a fragmented cutaway view of an example of acatheter with an annular channel and annular plug according to anembodiment of the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0030] In the following description of preferred embodiments, referenceis made to the accompanying drawings which form a part hereof, and inwhich is shown by way of illustration specific embodiments in which theinvention may be practiced. It is to be understood that otherembodiments may be utilized and structural changes may be made withoutdeparting from the scope of the preferred embodiments of the presentinvention.

[0031] As discussed above, the present invention relates generally to animproved catheter. Embodiments of the invention may be employed invarious infusion environments including, but not limited to a biologicalimplant environment. In preferred embodiments, a catheter is configuredfor an implant environment within a human body, as shown in FIG. 1.However, other embodiments may be employed in other biological implantor non-implant environments.

[0032]FIG. 2 illustrates an example of a catheter 20 according to onepreferred embodiment of the present invention. Catheter 20, shown in afragmented cutaway view in FIG. 2, may be used in conjunction with anIIP. Catheter 20 comprises a lumen 26 which extends through a barrierlayer 24 having a relative stiffness and density suitable for theenvironment of use. The material used for barrier layer 24 may beselected from the group of halogenated polymers such as, but not limitedto, polytetrafluorethylene (PTFE Teflon), polyvinylidene chloride(Saran), polyvinylidene fluoride (Kynar), or derivatives of any of thesematerials. Other suitable materials include polymeric materials such as,but not limited to, polyamides, ethylene-vinyl alcohol (EVOH),polyetheretherketone (PEEK), nylon, polyester, or derivatives of any ofthese materials. In addition, inorganic materials such as, but notlimited to, glass capillary tubing or diamond coated tubing may be usedfor the barrier layer 24. Catheter 20 also comprises an outer layer 22of soft, flexible, bio-compatible material such as, but not limited to,relatively soft silicone rubber or polyethylene.

[0033] In a preferred embodiment of the present invention, the outerlayer 22 is in firm contact with and substantially covers the barrierlayer 24. The outer layer 22 protrudes beyond the barrier layer 24 atthe distal end tip 23 a distance sufficient to cover the edge of thebarrier layer 24, as referenced by numeral 21. The soft material ofouter layer 22 preferably is formed to conform to and cover the edge ofthe barrier layer 24. This reduces irritation to the patient, as thebarrier layer 24 may be relatively rigid and may irritate tissue withwhich the tip comes into direct contact.

[0034] Preferably, the length of the protrusion of the outer layer 22beyond barrier layer 24 is selected to provide sufficient coverage ofthe edge of the barrier layer, but not so long as to allow significantdiffusion into or out of the infusion formulation prior to the infusionformulation being discharged from the distal end tip 23. Obstructions atthe distal end tip 23 may occur for at least three reasons. First,because the volume of the infusion formulation (such as an insulinformulation) situated in the distal end tip 23 has been present in thecatheter the longest period of time, it has been subjected to anydiffusion longer than the remainder of the infusion formulation presentin the catheter. Second, the volume of the infusion formulation situatedin the portion of the distal end tip 23 without the protection ofbarrier layer 24 will be more likely to encounter diffusing CO₂ andother substances. Third, stabilizers or preservatives may be lost bydiffusion and/or interaction with materials that mix with the infusionformulation through the opening at the distal end tip 23. Therefore, theportion of the outer layer 22 that protrudes beyond the barrier layer 24at the distal end tip 23 may provide an attachment site for obstructionsdue to lack of a barrier layer in that portion of the catheter 20.Accordingly, in some embodiments this portion may be kept to a minimum.

[0035] In a preferred embodiment of the present invention, in order tominimize the potential for obstructions, the distance that outer layer22 protrudes beyond barrier layer 24 may surround a volume no greaterthan the smallest possible pump stroke volume of the IIP, i.e., thesmallest possible amount of infusion formulation displaced per actuationof the IIP. This will result in a minimum exposure time for the infusionformulation in the unprotected portion of the distal end tip 23. In thealternative, the distance may be based on surrounding a volume nogreater than a volume corresponding to a predefined number of pumpstrokes.

[0036] Alternatively, the distance that outer layer 22 protrudes beyondbarrier layer 24 may fall within a possible range of distances. Inembodiments of the present invention, a range of distances betweenone-half inch to one inch may be used. In a preferred embodiment, thedistance for the protrusion of outer layer 22 beyond barrier layer 24may be one-half inch. Similarly, the ratio of protrusion length tothickness for outer layer 22 may fall within a possible range. Inembodiments of the present invention, a range of ratios between 0.5 and50 may be used. More preferably, a range between 1 and 20 may be used.Most preferably, a range between 1 and 10 may be used. In a preferredembodiment of the present invention, the ratio of length to thickness ofouter layer 22 may be one to one, i.e., the length of the protrusionbeyond the distal end tip 23, referenced by numeral 25, may be equal tothe thickness of the outer layer 22, referenced by numeral 27. Otherembodiments may employ other dimensions and ratios.

[0037] In a preferred embodiment of the present invention, catheter 20shown in FIG. 2 may be used to deliver Lispro or other forms of insulinformulation to the patient. It is believed that diffusion of CO₂ throughthe layers or up the distal end tip of the catheter leads toprecipitation and eventually to the formation of deposits that mayresult in catheter obstructions. Thus, in prior art catheters, Lisproand other forms of insulin formulation may be susceptible to theformation of obstructions due to the insufficient barriers thesecatheters provided against diffusion of CO₂ and other substances. Theseobstructions result in destabilization of the Lispro, and the Lispro maybe hindered in reaching the infusion site.

[0038] Preferred embodiments of the present invention significantlyreduce the amount of diffusion through the catheter layers by providinga barrier layer for the catheter. In embodiments of the presentinvention, the barrier layer may be made of a material that iscompatible with the environment of use (for example, infusionformulation compatible and, if necessary, bio-compatible andbio-stable). In a preferred embodiment of the present invention, thematerial of barrier layer 24 is PTFE Teflon and the undesirablesubstance is CO₂.

[0039] PTFE Teflon is chosen because it is insulin formulationcompatible, bio-compatible, bio-stable, and has a gas permeability indexfor CO₂ that is much lower than that of other materials commonly used ina catheter wall. The gas permeability index, in reference to a specifiedmaterial, indicates the ability of a specified gas to permeate throughthe material. For example, the gas permeability index of PTFE Teflon forCO₂ is 6.8 (cc-mm/sec-cm²-cmHg). In contrast, the gas permeability indexof polyethylene for CO₂ is 280 (cc-mm/sec-cm²-cmHg). Thus, the use ofPTFE Teflon as a CO₂ barrier can result in a barrier that is as much as40 times more effective than polyethylene, assuming the same dimensionsof the catheter. Thus, barrier layer 24 substantially hinders diffusionof CO₂ into the lumen of catheter 20.

[0040] An additional advantage to the use of PTFE Teflon in a catheteris its relative stiffness. This stiffness may facilitate the projectionof the catheter through the body. For example, in the intraperitonealdelivery of insulin formulation discussed above, the catheter isprojected through the peritoneal wall of a patient. The added stiffnessprovided by the PTFE Teflon may be beneficial for such uses of thecatheter.

[0041] A further preferred embodiment of the present invention has aflared or tapered distal end tip to aid in the release, during a bolusdelivery or catheter flush, of any deposited precipitated substancesituated at or near the distal end tip of the catheter. FIG. 3 shows afragmented cutaway view of catheter 30. Catheter 30 comprises a lumen 36which extends through a barrier layer 34 of relatively stiff, densematerial. The material used for barrier layer 34 may be selected fromthe group of halogenated polymers such as, but not limited to, PTFETeflon, Saran, Kynar, or derivatives of any of these materials. Othersuitable materials include polymeric materials such as, but not limitedto, polyamides, EVOH, PEEK, nylon, polyester, or derivatives of any ofthese materials. In addition, inorganic materials such as, but notlimited to, glass capillary tubing or diamond coated tubing may be usedfor the barrier layer 34. Catheter 30 further comprises an outer layer32 of soft, flexible, bio-compatible material such as, but not limitedto, relatively soft silicone rubber or polyethylene.

[0042] In a preferred embodiment of the present invention, the outerlayer 32 is in firm contact with and substantially covers the barrierlayer 34. The outer layer 32 protrudes beyond the barrier layer 34 atthe distal end tip 33 of catheter 30 a distance sufficient to cover theedge of the barrier layer 34. As discussed above in reference to FIG. 2,the soft material of outer layer 32 preferably is formed to conform toand cover the edge of the barrier layer 34.

[0043] Beginning at a specified distance from the distal end tip 33,referred to in the present application as the “apex” 38, the innercross-sectional diameter of the lumen 36, bounded by barrier layer 34,becomes progressively larger as it extends toward the distal end is tip33. This results in the flaring of the lumen 36 as it extends from theapex 38 towards the distal end tip 33. The inner cross-sectionaldiameter of the lumen 36 increases but, in preferred embodiments, theouter cross-sectional diameter of the lumen 36 remains relativelyconstant. Thus, it is easier to pass catheter 30 through small incisionsand irritation is reduced.

[0044] In embodiments of the present invention, the cross-sectionaldiameter of the portion of the lumen 36 that extends from the apex 38towards the proximal end 39, i.e., the un-flared portion of the lumen36, may be about 0.007 inch. In a preferred embodiment of the presentinvention the distance of apex 38 from distal end tip 33 may beapproximately 0.5 inch. The lumen 36 will continue to flare as itprogresses to the distal end tip 33. In embodiments of the presentinvention, the cross-sectional diameter of the lumen 36 at its widestpoint, i.e., at the distal end tip 33, may be about 0.020 inch. Otherembodiments may employ other dimensions.

[0045] The larger cross-sectional area at the distal end tip 33minimizes the chances that any obstruction that develops at or near thedistal end tip 33 will be sufficient to hinder the flow of the infusionformulation within the lumen 36. In addition, deposits that do form inthe flared portion of distal end tip 33 are more likely to be expelledduring a bolus delivery or catheter flush due to the shape and largercross-sectional area of the flare. Other shapes besides a flare shapefor the distal end tip 33 are also possible. For example, the transitionto a larger cross-sectional area of the inner surface of the lumen 36may take place more abruptly with a more uniformly cylindrical shape forthe widened portion of lumen 36 nearest the distal end tip 33.

[0046] The flared or tapered shape of the distal end tip 33 has anotheradvantage. During the interval between IIP pump strokes, body fluidswill mix with the infusion formulation present at the distal end tip 33.The area of the lumen 36 into which the body fluids will penetrate isreferred to as the “mixing zone.” The potential for the formation ofobstructions in the mixing zone is high due to the mixing of substanceswithin the body fluids with substances within the insulin formulation.

[0047] The flared or tapered distal end tip 33 of the embodiment of thepresent invention illustrated in FIG. 3 greatly reduces the potentialfor complete obstructions by selecting the distance of the apex 38 fromthe distal end tip 33 such that the mixing zone of the lumen 36 iscontained within the flare. Because the mixing zone is contained withinthe larger diameter of the flare and not within the smaller diameter ofthe remainder of the lumen 36, the potential for complete obstructionsresulting from the mixing of body fluids with the insulin formulation isgreatly reduced.

[0048] Another preferred embodiment of the present invention furtherreduces potential for obstructions in the mixing zone by providing aslit valve to cover the distal end tip of the catheter to prevent bodyfluids from entering the mixing zone during the interval between IIPpump strokes. FIG. 4 shows a fragmented cutaway view of catheter 40.Catheter 40 comprises a lumen 46 which extends through a barrier layer44 of relatively stiff, dense material. The material used for barrierlayer 44 may be selected from the group of halogenated polymers such as,but not limited to, PTFE Teflon, Saran, Kynar, or derivatives of any ofthese materials. Other suitable materials include polymeric materialssuch as, but not limited to, polyamides, EVOH, PEEK, nylon, polyester,or derivatives of any of these materials. In addition, inorganicmaterials such as, but not limited to, glass capillary tubing or diamondcoated tubing may be used for the barrier layer 44. Catheter 40 furthercomprises an outer layer 42 of soft, flexible, bio-compatible materialsuch as, but not limited to, relatively soft silicone rubber orpolyethylene.

[0049] In a preferred embodiment of the present invention, the outerlayer 42 is in firm contact with and substantially covers the barrierlayer 44. The outer layer 42 protrudes beyond the barrier layer 44 atthe distal end tip 43 a sufficient amount to form slit valve 45. Slitvalve 45 has a semi-spherical shape. Other shapes are also possible. Forexample, slit valve 45 could have a conical shape with thecross-sectional area gradually narrowing from the distal end tip 43outward. Slit valve 45 has a slit 48 that may be elastically extended toan open position by the expulsion of the infusion formulation during anIIP pump stroke. During the interval between IIP pump strokes, the slit48 will elastically return to a closed position and hinder the inflow ofbody fluids. Thus, slit valve 45 greatly reduces the potential for theformation of obstructions resulting from the mixing of body fluids withthe infusion formulation during the interval between IIP pump strokes.

[0050] In other preferred embodiments, slit valve 45 may comprise one ormore and, preferably a plurality of slits. Also, the slits may bepositioned at various points on the slit valve, for example, along thesides of the slit valve. Further, the slit valve may also be utilized ina non-flared catheter such as the catheter discussed above in relationto FIG. 2.

[0051] A further preferred embodiment of the present invention providesalternate paths for the flow of the infusion formulation out of thedistal end tip in the event that the tip becomes blocked. FIG. 5 shows afragmented cutaway view of catheter 50. Catheter 50 comprises a lumen 56which extends through a barrier layer 54 of relatively stiff, densematerial. The material used for barrier layer 54 may be selected fromthe group of halogenated polymers such as, but not limited to, PTFETeflon, Saran, Kynar, or derivatives of any of these materials. Othersuitable materials include polymeric materials such as, but not limitedto, polyamides, EVOH, PEEK, nylon, polyester, or derivatives of any ofthese materials. In addition, inorganic materials such as, but notlimited to, glass capillary tubing or diamond coated tubing may be usedfor the barrier layer 54. Catheter 50 also comprises an outer layer 52of soft, flexible, bio-compatible material such as, but not limited to,relatively soft silicone rubber or polyethylene.

[0052] In a preferred embodiment of the present invention, the outerlayer 52 is in firm contact with and substantially covers the barrierlayer 54. The outer layer 52 protrudes beyond the barrier layer 54 atthe distal end tip 53 a distance sufficient to cover the edge of thebarrier layer 54. The soft material of outer layer 52 preferably isformed to conform to and cover the edge of the barrier layer 54.Flowholes 55 are formed in barrier layer 54 to allow the infusionformulation to flow through an annular channel 58, the entrance intowhich is formed between the outer surface of barrier layer 54 and theinner surface of outer layer 52 at a specified distance, referred to bynumeral 59, from the distal end tip 53. The distance is chosen such thatthe entrance into the annular channel 58 will be sufficiently upstreamfrom the mixing zone and, thus, from any obstruction. In a preferredembodiment of the present invention, distance 59 is approximately 0.50inch from the distal end tip 53. Other embodiments may employ otherdistances.

[0053] If an obstruction 57 forms at the distal end tip 53, the pressureof the outward flow of the infusion formulation during an IIP pumpstroke will be sufficient to elastically separate the outer surface ofthe barrier layer 54 from the inner surface of the outer layer 52 alongthe annular channel 58, providing a passageway for the infusionformulation. Thus, the infusion formulation will flow around theobstruction 57 and to the infusion site, as shown by directed arrows 51.In the interval between IIP pump strokes, the outer surface of thebarrier layer 54 will elastically return to contact the inner surface ofthe outer layer 52 along the annular channel 58.

[0054] An example of an alternative preferred embodiment of the presentinvention is shown in FIG. 6. FIG. 6 shows catheter 60. Catheter 60comprises a lumen 66 which extends through a barrier layer 64 ofrelatively stiff, dense material. The material used for barrier layer 64may be selected from the group of halogenated polymers such as, but notlimited to, PTFE Teflon, Saran, Kynar, or derivatives of any of thesematerials. Other suitable materials include polymeric materials such as,but not limited to, polyamides, EVOH, PEEK, nylon, polyester, orderivatives of any of these materials. In addition, inorganic materialssuch as, but not limited to, glass capillary tubing or a diamond coatedtubing may be used for the barrier layer 64. Catheter 60 also comprisesan outer layer 62 of soft, flexible, bio-compatible material such as,but not limited to, relatively soft silicone rubber or polyethylene.

[0055] In a preferred embodiment of the present invention, the outerlayer 62 is in firm contact with and substantially covers the barrierlayer 64. The outer layer 62 protrudes beyond the barrier layer 64 atthe distal end tip 63 a distance sufficient to cover the edge of thebarrier layer 64. The soft material of outer layer 62 preferably isformed to conform to and cover the edge of the barrier layer 64.

[0056] Flowholes 65 are formed in barrier layer 64 and outer layer 62 toallow the infusion formulation to flow through an annular channel 69,the entrance into which is formed between annular plug 68 and the outersurface of outer layer 62. Annular plug 68 is disposed over flowholes65. Annular plug 68 may be a soft, flexible, bio-compatible materialsuch as, but not limited to, relatively soft silicone rubber orpolyethylene. Annular plug 68 provides an adequate seal against outflowthrough flowholes 65 of the infusion formulation within lumen 66 undernormal pressure. However, if an obstruction, referred to by numeral 67,develops at or near the distal end tip 63, then the pressure of theoutward flow of the infusion formulation during an IIP pump stroke willbe sufficient to elastically separate the inner surface of the annularplug 68 from the outer surface of the outer layer 62, providing apassageway for the infusion formulation through annular channel 69.Thus, the infusion formulation will flow around the obstruction 67 andto the infusion site, as shown by directed arrows 61. During theinterval between IIP pump strokes, the inner surface of the annular plug68 will elastically return to the outer surface of the outer layer 62.

[0057] In all of the preferred embodiments of the present inventiondiscussed above, an additional interior layer may be provided on theinner surface of the barrier layer. The material provided for theinterior layer may be hydrophobic or hydrophilic in nature in order toregulate the interaction of infusion formulation components with theinterior surface. The interior catheter surface may also contain or betreated to contain chemical groups that permit the covalent or physicalattachment of compounds that will regulate its surface properties andpermeability.

[0058] Further, in preferred embodiments of the present invention thebarrier layer may be sandwiched between layers of bio-compatiblematerial such as, but not limited to, polyethylene and silicone rubber.Thus, the barrier layer will continue to provide a barrier againstdiffusion of substances into or out of the catheter. In someapplications, the barrier layer may be the outermost layer of thecatheter.

[0059] Furthermore, in some applications, it may be determined that theadvantages of the invention's barrier layer described above are onlyrequired in a portion of the catheter. Thus, in some embodiments of theinvention's catheter the barrier layer is used in only that portion ofthe catheter where the described advantages are most needed. In theseembodiments, the remainder of the catheter may not comprise any barrierlayer material.

[0060] In yet other applications, it may be advantageous to cover only aportion of the barrier layer material with the outer layer material.Thus, in some embodiments, the outer layer material covers only thoseportions of the barrier layer material where the advantages of the outerlayer material (for example, softness and/or flexibility) are mostneeded, for example, at the distal end tip.

[0061] Catheter structures in accordance with various embodiments of theinvention may be manufactured in any suitable manner, including, but notlimited to, extruding or molding inner and outer layers together orseparately.

[0062] Therefore, embodiments of the present invention provide acatheter which provides a significant barrier to diffusion of CO₂ andother substances into the lumen of the catheter. A barrier layer isprovided as part of the catheter which inhibits the outward diffusion ofsubstances flowing through the lumen of the catheter. Thus, theproperties, composition, and/or stability of the infusion formulationdelivered to the infusion site may be more accurately controlled.

[0063] Embodiments of the present invention also provide a catheterwhich inhibits deposit formation at the distal end tip and facilitatesthe expulsion during delivery, for example, delivery of a bolus orcatheter flush The larger cross-sectional area of the flare at thedistal end tip aids in the release, during a bolus delivery or catheterflush, of deposited precipitated substances situated at the distal endtip of the catheter and minimizes the chances that any obstruction thatdevelops at the distal end tip will be sufficient to hinder the flow ofthe infusion formulation within the lumen of the catheter to theinfusion site.

[0064] Embodiments of the present invention also provide a catheterwhich inhibits deposit formation at the distal end tip by providing aslit valve at the distal end tip. The slit valve has one or more and,preferably a plurality of slits that may be elastically extended to anopen position by the expulsion of the infusion formulation during an IIPpump stroke. During the interval between IIP pump strokes, the slitswill return to a closed position and hinder the inflow of body fluidinto the distal end tip.

[0065] Embodiments of the present invention also provide a catheterwhich provides an annular channel. This annular channel may be formed inthe catheter at a sufficient upstream distance from the distal end tipto provide an alternate passageway for the infusion formulation to theinfusion site through the annular channel in the event of anobstruction.

[0066] Thus, embodiments of the present invention provide a catheterwhich inhibits diffusion of substances through the layers of thecatheter and which minimizes the chances that the flow of infusionformulations through the catheter will be blocked.

[0067] While particular embodiments of the present invention have beenshown and described, it will be obvious to those skilled in the art thatthe invention is not limited to the particular embodiments shown anddescribed and that changes and modifications may be made withoutdeparting from the spirit and scope of the appended claims.

What is claimed is:
 1. A catheter for use in conveyance of aformulation, the catheter comprising: first and second materialsconfigured to define a tubular structure, the tubular structure having aproximal and a distal end; wherein the second material has apermeability lower than polyethylene for at least one substance thatcould cause detrimental change in the properties or composition of theformulation.
 2. The catheter as recited in claim 1, wherein the firstmaterial is disposed outside the second material.
 3. The catheter asrecited in claim 1, wherein the first material is disposed inside thesecond material.
 4. The catheter as recited in claim 1, wherein thesecond material comprises a material that has a permeability index forthe at least one substance that is lower than the permeability index ofthe outer material for the at least one substance.
 5. The catheter asrecited in claim 4, wherein the at least one substance comprises CO₂ andwherein the detrimental change occurs as a result of diffusion of theCO₂ into the catheter.
 6. The catheter as recited in claim 4, whereinthe at least one substance comprises phenolic compounds and wherein thedetrimental change occurs as a result of diffusion of the phenoliccompounds out of the catheter.
 7. The catheter as recited in claim 6,wherein the phenolic compounds comprise at least one of phenol andm-cresol.
 8. The catheter as recited in claim 1, wherein the secondmaterial comprises a material selected from the group consisting ofhalogenated polymers.
 9. The catheter as recited in claim 8, wherein thehalogenated polymer is selected from the group essentially consisting ofpolytetrafluorethylene, polyvinylidene chloride and polyvinylidenefluoride.
 10. The catheter as recited in claim 1, wherein the secondmaterial comprises a material selected from the group consistingessentially of polyamides, ethylene-vinyl alcohol, polyetheretherketone,nylon and polyester.
 11. The catheter as recited in claim 1, wherein thesecond material is capillary glass.
 12. The catheter as recited in claim1, wherein the second material is diamond coated.
 13. The catheter asrecited in claim 1, wherein the first material comprises a material thatis bio-compatible.
 14. The catheter as recited in claim 2, wherein aninner surface of the first material substantially covers an outersurface of the second material.
 15. The catheter as recited in claim 2,wherein an inner surface of the first material covers only a portion ofan outer surface of the second material.
 16. The catheter as recited inclaim 15, wherein the portion of the outer surface of the secondmaterial covered by the inner surface of the first material is locatedat the distal end.
 17. The catheter as recited in claim 1, furthercomprising an interior layer contacting an inner surface of the secondmaterial, the interior layer comprising a substance that regulates aninteraction of substances with the interior layer.
 18. The catheter asrecited in claim 17, wherein the substance is a hydrophilic substance.19. The catheter as recited in claim 17, wherein the substance is ahydrophobic substance.
 20. The catheter as recited in claim 1, whereinan inner diameter of the distal end has a flared shape.
 21. The catheteras recited in claim 20, wherein an outer diameter of the distal end issubstantially constant across the flared shape.
 22. The catheter asrecited in claim 1, wherein the proximal end is connected to animplantable infusion pump.
 23. The catheter as recited in claim 1,wherein the first material is more flexible than the second material.24. The catheter as recited in claim 1, wherein the first material has alower flexural modulus than the second material.
 25. A catheter for usein delivery of a formulation, the catheter comprising: an outer layercomprising an outer surface and an inner surface; a barrier layercomprising an outer surface and an inner surface; a proximal end; and adistal end having a surface on which an obstruction may form; whereinthe barrier layer further comprises flowholes formed therein at asufficient upstream distance from any obstruction formed at the distalend, the flowholes providing entry into an annular channel located onthe downstream side of the flowholes, the annular channel being boundedby a portion of the inner surface of the outer layer and a portion ofthe outer surface of the barrier layer, the annular channel providing apassageway out of the catheter for the formulation in the event of anobstruction, the portion of the inner surface of the outer layer, undersufficient pressure, elastically separating from the portion of theouter surface of the barrier layer to complete the passageway.
 26. Thecatheter as recited in claim 25, wherein the inner surface of the outerlayer substantially covers the outer surface of the barrier layer. 27.The catheter as recited in claim 25, wherein the inner surface of theouter layer covers only a portion of the outer surface of the barrierlayer.
 28. The catheter as recited in claim 27, wherein the portion ofthe outer surface of the barrier layer covered by the inner surface ofthe outer layer is located at the distal end.
 29. The catheter asrecited in claim 25, wherein an inner diameter of the distal end has aflared shape.
 30. The catheter as recited in claim 29, wherein a n outerdiameter o f the distal end is substantially constant across the flaredshape.
 31. A catheter for use in delivery of a formulation, the cathetercomprising: an outer layer comprising an outer surface and an innersurface, a portion of the outer surface further comprising an annularplug having an outer surface and an inner surface; a barrier layercomprising an outer surface and an inner surface; a proximal end; and adistal end having a surface on which an obstruction may form; whereinthe barrier layer and the outer layer further comprise flowholes formedjointly therein at a sufficient upstream distance from any obstructionformed at the distal end, the flowholes providing entry into an annularchannel located on the downstream side of the flowholes, the annularchannel being bounded by a portion of the inner surface of the annularplug and a portion of the outer surface of the outer layer, the annularchannel providing a passageway out of the catheter for the formulationin the event of an obstruction, the portion of the inner surface of theannular plug, under sufficient pressure, elastically separating from theportion of the outer surface of the outer layer to complete thepassageway.
 32. The catheter as recited in claim 31, wherein the annularplug comprises a material that is bio-compatible.
 33. The catheter asrecited in claim 31, wherein the inner surface of the outer layersubstantially covers the outer surface of the barrier layer.
 34. Thecatheter as recited in claim 31, wherein the inner surface of the outerlayer covers only a portion of the outer surface of the barrier layer.35. The catheter as recited in claim 31, wherein the portion of theouter surface of the barrier layer covered by the inner surface of theouter layer is located at the distal end.
 36. The catheter as recited inclaim 31, wherein an inner diameter of the distal end has a flaredshape.
 37. The catheter as recited in claim 36, wherein an outerdiameter of the distal end is substantially constant across the flaredshape.
 38. A catheter for use in conveyance of a formulation, thecatheter comprising: an outer material; an inner barrier material; aproximal end; and a distal end; wherein the outer material protrudes adistance beyond the inner barrier material at the distal end and forms agenerally semi spherical segment spaced from and enclosing the distalend, the semi spherical segment comprising at least one slit formedthereon, the at least one slit expanding upon a pump stroke of aninfusion pump to release the formulation and closing at an intervalbetween pump strokes to hinder inflow of substances into the distal endof the catheter.
 39. The catheter as recited in claim 38, wherein theinner surface of the outer material substantially covers the outersurface of the inner barrier material.
 40. The catheter as recited inclaim 38, wherein the inner surface of the outer material covers only aportion of the outer surface of the inner barrier material.
 41. Thecatheter as recited in claim 40, wherein the portion of the outersurface of the inner barrier material covered by the inner surface ofthe outer material is located at the distal end.
 42. The catheter asrecited in claim 38, wherein an inner diameter of the distal end has aflared shape.
 43. The catheter as recited in claim 42, wherein an outerdiameter of the distal end is substantially constant across the flaredshape.
 44. An implantable infusion pump system for use in delivery of aformulation, the system comprising: a pump for delivering measured dosesof a formulation; a sensing device for regulating the delivery of theformulation; and a catheter for conveying the formulation from the pumpto an infusion site, the catheter comprising: an outer material; aninner barrier material; a proximal end attached to the pump; and adistal end located at the infusion site; wherein the barrier materialhas a permeability lower than polyethylene for at least one substancethat could cause detrimental change in the properties or composition ofthe formulation.
 45. An implantable infusion pump system for use indelivery of a formulation, the system comprising: a pump for deliveringmeasured doses of a formulation; a sensing device for regulating thedelivery of the formulation; and a catheter for conveying theformulation from the pump to an infusion site, the catheter tocomprising: an outer layer comprising an outer surface and an innersurface; a barrier layer comprising an outer surface and an innersurface; a proximal end attached to the pump; and a distal end locatedat the infusion site, the distal end having a surface on which anobstruction may form; wherein the barrier layer further comprisesflowholes formed therein at a sufficient upstream distance from anyobstruction formed at the distal end, the flowholes providing entry intoan annular channel located on the downstream side of the flowholes, theannular channel being bounded by a portion of the inner surface of theouter layer and a portion of the outer surface of the barrier layer, theannular channel providing a passageway out of the catheter for theformulation in the event of an obstruction, the portion of the innersurface of the outer layer, under sufficient pressure, elasticallyseparating from the portion of the outer surface of the barrier layer tocomplete the passageway.
 46. An implantable infusion pump system for usein delivery of a formulation, the system comprising: a pump fordelivering measured doses of a formulation; a sensing device forregulating the delivery of the formulation; and a catheter for conveyingthe formulation from the pump to an infusion site, the cathetercomprising: an outer layer comprising an outer surface and an innersurface, a portion of the outer surface further comprising an annularplug having an outer surface and an inner surface; a barrier layercomprising an outer surface and an inner surface; a proximal end; and adistal end having a surface on which an obstruction may form; whereinthe barrier layer and the outer layer further comprise flowholes formedjointly therein at a sufficient upstream distance from any obstructionformed at the distal end, the flowholes providing entry into an annularchannel located on the downstream side of the flowholes, the annularchannel being bounded by a portion of the inner surface of the annularplug and a portion of the outer surface of the outer layer, the annularchannel providing a passageway out of the catheter for the formulationin the event of an obstruction, the portion of the inner surface of theannular plug, under sufficient pressure, elastically separating from theportion of the outer surface of the outer layer to complete thepassageway.
 47. An implantable infusion pump system for use in deliveryof a formulation, the system comprising: a pump for delivering measureddoses of a formulation; a sensing device for regulating the delivery ofthe formulation; and a catheter for conveying the formulation from thepump to an infusion site, the catheter comprising: a proximal endattached to the pump; and a distal end located at the infusion site;wherein the catheter comprises a material having a permeability lowerthan polyethylene for at least one substance that could causedetrimental change in the properties or composition of the formulation.48. The implantable infusion pump system as recited in claim 47, whereinthe material comprises a material selected from the group consisting ofhalogenated polymers.
 49. The implantable infusion pump system asrecited in claim 48, wherein the halogenated polymer is selected fromthe group essentially consisting of polytetrafluorethylene,polyvinylidene chloride and polyvinylidene fluoride.
 50. The implantableinfusion pump system as recited in claim 47, wherein the materialcomprises a material selected from the group consisting essentially ofpolyamides, ethylene-vinyl alcohol, polyetheretherketone, nylon andpolyester.
 51. The implantable infusion pump system as recited in claim47, wherein the material is capillary glass.
 52. The implantableinfusion pump system as recited in claim 47, wherein the material is adiamond coated material.
 53. A catheter for use in conveyance of aformulation, the catheter comprising: an outer material; an innermaterial; a proximal end; and a distal end; wherein at least one of theouter material and the inner material has a permeability lower thanpolyethylene for at least one substance that could cause detrimentalchange in the properties or composition of the formulation.
 54. Acatheter for use in delivery of a formulation, the catheter comprising:an outer layer comprising an outer surface and an inner surface; abarrier layer comprising an outer surface and an inner surface; aproximal end; and a distal end; wherein the inner surface of the outerlayer covers the outer surface of the barrier layer only at the distalend of the catheter.